data_20087 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; Novel Helix-Constrained Nociceptin Derivatives Are Potent Agonists and Antagonists of ERK Phosphorylation and Thermal Analgesia in Mice ; _BMRB_accession_number 20087 _BMRB_flat_file_name bmr20087.str _Entry_type new _Submission_date 2009-07-23 _Accession_date 2009-07-23 _Entry_origination author _NMR_STAR_version 2.1.1 _Experimental_method NMR _Details . loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Fairlie David P. . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count assigned_chemical_shifts 1 coupling_constants 1 stop_ loop_ _Data_type _Data_type_count "1H chemical shifts" 121 "coupling constants" 17 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2011-07-08 update BMRB 'update entry citation' 2011-06-03 original author 'orginial release' stop_ loop_ _Related_BMRB_accession_number _Relationship 20086 'nociceptin Antagonist' 20088 'nociceptin analogue' 20089 'nociceptin analogue' stop_ save_ ############################# # Citation for this entry # ############################# save_entry_citation _Saveframe_category entry_citation _Citation_full . _Citation_title 'Novel Helix-Constrained Nociceptin Derivatives Are Potent Agonists and Antagonists of ERK Phosphorylation and Thermal Analgesia in Mice.' _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 21067234 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Harrison Rosemary S. . 2 Ruiz-Gomez Gloria . . 3 Hill Timothy A. . 4 Chow Shiao Y. . 5 Shepherd Nicholas E. . 6 Lohman Rink-Jan . . 7 Abbenante Giovanni . . 8 Hoang Huy N. . 9 Fairlie David P. . stop_ _Journal_abbreviation 'J. Med. Chem.' _Journal_name_full 'Journal of medicinal chemistry' _Journal_volume 53 _Journal_issue 23 _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first 8400 _Page_last 8408 _Year 2010 _Details . save_ ################################## # Molecular system description # ################################## save_assembly _Saveframe_category molecular_system _Mol_system_name 'nociceptin analogue' _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label 'nociceptin analogue' $nociceptin_analogue stop_ _System_molecular_weight . _System_physical_state native _System_oligomer_state ? _System_paramagnetic no _System_thiol_state . _Database_query_date . _Details . save_ ######################## # Monomeric polymers # ######################## save_nociceptin_analogue _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class protein _Name_common nociceptin_analogue _Molecular_mass . _Mol_thiol_state 'not present' _Details . ############################## # Polymer residue sequence # ############################## _Residue_count 19 _Mol_residue_sequence FGGXTGKRKSDRKKKNQDX loop_ _Residue_seq_code _Residue_label 1 PHE 2 GLY 3 GLY 4 PFF 5 THR 6 GLY 7 LYS 8 ARG 9 LYS 10 SER 11 ASP 12 ARG 13 LYS 14 LYS 15 LYS 16 ASN 17 GLN 18 ASP 19 NH2 stop_ _Sequence_homology_query_date . _Sequence_homology_query_revised_last_date 2015-06-22 loop_ _Database_name _Database_accession_code _Database_entry_mol_name _Sequence_query_to_submitted_percentage _Sequence_subject_length _Sequence_identity _Sequence_positive _Sequence_homology_expectation_value BMRB 20088 nociceptin_analogue 94.74 19 100.00 100.00 7.88e-01 BMRB 20089 nociceptin_analogue 94.74 19 100.00 100.00 7.88e-01 stop_ save_ ###################### # Polymer residues # ###################### save_chem_comp_PFF _Saveframe_category polymer_residue _Mol_type 'L-peptide linking' _Name_common 4-FLUORO-L-PHENYLALANINE _BMRB_code . _PDB_code PFF _Standard_residue_derivative . _Molecular_mass 183.180 _Mol_paramagnetic . _Details ; Information obtained from PDB's Chemical Component Dictionary at http://wwpdb-remediation.rutgers.edu/downloads.html Downloaded on Tue Jun 9 15:44:06 2009 ; loop_ _Atom_name _PDB_atom_name _Atom_type _Atom_chirality _Atom_charge _Atom_oxidation_number _Atom_unpaired_electrons N N N . 0 . ? CA CA C . 0 . ? C C C . 0 . ? O O O . 0 . ? OXT OXT O . 0 . ? CB CB C . 0 . ? CG CG C . 0 . ? CD1 CD1 C . 0 . ? CD2 CD2 C . 0 . ? CE1 CE1 C . 0 . ? CE2 CE2 C . 0 . ? CZ CZ C . 0 . ? F F F . 0 . ? H H H . 0 . ? H2 H2 H . 0 . ? HA HA H . 0 . ? HXT HXT H . 0 . ? HB2 HB2 H . 0 . ? HB3 HB3 H . 0 . ? HD1 HD1 H . 0 . ? HD2 HD2 H . 0 . ? HE1 HE1 H . 0 . ? HE2 HE2 H . 0 . ? stop_ loop_ _Bond_order _Bond_atom_one_atom_name _Bond_atom_two_atom_name _PDB_bond_atom_one_atom_name _PDB_bond_atom_two_atom_name SING N CA ? ? SING N H ? ? SING N H2 ? ? SING CA C ? ? SING CA CB ? ? SING CA HA ? ? DOUB C O ? ? SING C OXT ? ? SING OXT HXT ? ? SING CB CG ? ? SING CB HB2 ? ? SING CB HB3 ? ? DOUB CG CD1 ? ? SING CG CD2 ? ? SING CD1 CE1 ? ? SING CD1 HD1 ? ? DOUB CD2 CE2 ? ? SING CD2 HD2 ? ? DOUB CE1 CZ ? ? SING CE1 HE1 ? ? SING CE2 CZ ? ? SING CE2 HE2 ? ? SING CZ F ? ? stop_ save_ save_chem_comp_NH2 _Saveframe_category polymer_residue _Mol_type non-polymer _Name_common 'AMINO GROUP' _BMRB_code . _PDB_code NH2 _Standard_residue_derivative . _Molecular_mass 16.023 _Mol_paramagnetic . _Details ; Information obtained from PDB's Chemical Component Dictionary at http://wwpdb-remediation.rutgers.edu/downloads.html Downloaded on Fri Jun 3 11:00:29 2011 ; loop_ _Atom_name _PDB_atom_name _Atom_type _Atom_chirality _Atom_charge _Atom_oxidation_number _Atom_unpaired_electrons N N N . 0 . ? HN1 HN1 H . 0 . ? HN2 HN2 H . 0 . ? stop_ loop_ _Bond_order _Bond_atom_one_atom_name _Bond_atom_two_atom_name _PDB_bond_atom_one_atom_name _PDB_bond_atom_two_atom_name SING N HN1 ? ? SING N HN2 ? ? stop_ save_ #################### # Natural source # #################### save_natural_source _Saveframe_category natural_source loop_ _Mol_label _Organism_name_common _NCBI_taxonomy_ID _Superkingdom _Kingdom _Genus _Species $nociceptin_analogue Human 9606 Eukaryota Metazoa Homo Sapiens stop_ save_ ######################### # Experimental source # ######################### save_experimental_source _Saveframe_category experimental_source loop_ _Mol_label _Production_method _Host_organism_name_common _Genus _Species _Strain _Vector_name $nociceptin_analogue 'chemical synthesis' . . . . . stop_ save_ ##################################### # Sample contents and methodology # ##################################### ######################## # Sample description # ######################## save_sample_1 _Saveframe_category sample _Sample_type solution _Details . loop_ _Mol_label _Concentration_value _Concentration_value_units _Concentration_min_value _Concentration_max_value _Isotopic_labeling $nociceptin_analogue . mM 2 5 'natural abundance' H2O 90 % . . 'natural abundance' D2O 10 % . . 'natural abundance' stop_ save_ ############################ # Computer software used # ############################ save_X-PLOR_NIH _Saveframe_category software _Name X-PLOR_NIH _Version . loop_ _Vendor _Address _Electronic_address 'Schwieters, Kuszewski, Tjandra and Clore' . . stop_ loop_ _Task 'geometry optimization' stop_ _Details . save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer Bruker _Model Avance _Field_strength 600 _Details . save_ ############################# # NMR applied experiments # ############################# save_2D_1H-1H_NOESY_1 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-1H NOESY' _Sample_label $sample_1 save_ save_2D_1H-1H_TOCSY_2 _Saveframe_category NMR_applied_experiment _Experiment_name '2D 1H-1H TOCSY' _Sample_label $sample_1 save_ save_2D_DQF-COSY_3 _Saveframe_category NMR_applied_experiment _Experiment_name '2D DQF-COSY' _Sample_label $sample_1 save_ ####################### # Sample conditions # ####################### save_sample_conditions_1 _Saveframe_category sample_conditions _Details . loop_ _Variable_type _Variable_value _Variable_value_error _Variable_value_units temperature 288 . K pH 4.5 . pH stop_ save_ #################### # NMR parameters # #################### ############################## # Assigned chemical shifts # ############################## ################################ # Chemical shift referencing # ################################ save_chemical_shift_reference_1 _Saveframe_category chemical_shift_reference _Details . loop_ _Mol_common_name _Atom_type _Atom_isotope_number _Atom_group _Chem_shift_units _Chem_shift_value _Reference_method _Reference_type _External_reference_sample_geometry _External_reference_location _External_reference_axis _Indirect_shift_ratio DSS H 1 'methyl protons' ppm 0 internal direct . . . 1.0000 stop_ save_ ################################### # Assigned chemical shift lists # ################################### ################################################################### # Chemical Shift Ambiguity Index Value Definitions # # # # The values other than 1 are used for those atoms with different # # chemical shifts that cannot be assigned to stereospecific atoms # # or to specific residues or chains. # # # # Index Value Definition # # # # 1 Unique (including isolated methyl protons, # # geminal atoms, and geminal methyl # # groups with identical chemical shifts) # # (e.g. ILE HD11, HD12, HD13 protons) # # 2 Ambiguity of geminal atoms or geminal methyl # # proton groups (e.g. ASP HB2 and HB3 # # protons, LEU CD1 and CD2 carbons, or # # LEU HD11, HD12, HD13 and HD21, HD22, # # HD23 methyl protons) # # 3 Aromatic atoms on opposite sides of # # symmetrical rings (e.g. TYR HE1 and HE2 # # protons) # # 4 Intraresidue ambiguities (e.g. LYS HG and # # HD protons or TRP HZ2 and HZ3 protons) # # 5 Interresidue ambiguities (LYS 12 vs. LYS 27) # # 6 Intermolecular ambiguities (e.g. ASP 31 CA # # in monomer 1 and ASP 31 CA in monomer 2 # # of an asymmetrical homodimer, duplex # # DNA assignments, or other assignments # # that may apply to atoms in one or more # # molecule in the molecular assembly) # # 9 Ambiguous, specific ambiguity not defined # # # ################################################################### save_assigned_chem_shift_list_1 _Saveframe_category assigned_chemical_shifts _Details 'NMR structure has been calculated by using PHE at the fourth position as opposed to PFF due to the absence of this residue in X-PLOR' loop_ _Experiment_label '2D 1H-1H NOESY' '2D 1H-1H TOCSY' '2D DQF-COSY' stop_ loop_ _Sample_label $sample_1 stop_ _Sample_conditions_label $sample_conditions_1 _Chem_shift_reference_set_label $chemical_shift_reference_1 _Mol_system_component_name 'nociceptin analogue' _Text_data_format . _Text_data . loop_ _Atom_shift_assign_ID _Residue_author_seq_code _Residue_seq_code _Residue_label _Atom_name _Atom_type _Chem_shift_value _Chem_shift_value_error _Chem_shift_ambiguity_code 1 1 1 PHE HA H 4.21 0.025 1 2 1 1 PHE HB2 H 3.11 0.0035 2 3 1 1 PHE HB3 H 3.14 0.0035 2 4 1 1 PHE HD1 H 7.21 0.0035 1 5 1 1 PHE HD2 H 7.21 0.0035 1 6 1 1 PHE HE1 H 7.31 0.0035 1 7 1 1 PHE HE2 H 7.31 0.0035 1 8 1 1 PHE HZ H 7.25 0.0035 1 9 2 2 GLY H H 8.60 0.0035 1 10 2 2 GLY HA2 H 3.83 0.025 1 11 2 2 GLY HA3 H 3.83 0.025 1 12 3 3 GLY H H 7.95 0.0035 1 13 3 3 GLY HA2 H 3.80 0.025 1 14 3 3 GLY HA3 H 3.80 0.025 1 15 4 4 PFF H H 8.33 0.0035 1 16 4 4 PFF HA H 4.59 0.025 1 17 4 4 PFF HB2 H 2.96 0.0035 2 18 4 4 PFF HB3 H 3.02 0.0035 2 19 4 4 PFF HD1 H 7.16 0.0035 1 20 4 4 PFF HD2 H 7.16 0.0035 1 21 4 4 PFF HE1 H 6.98 0.0035 1 22 4 4 PFF HE2 H 6.98 0.0035 1 23 5 5 THR H H 8.19 0.0035 1 24 5 5 THR HA H 4.16 0.025 1 25 5 5 THR HB H 4.12 0.025 1 26 5 5 THR HG2 H 1.11 0.0035 1 27 6 6 GLY H H 8.12 0.0035 1 28 6 6 GLY HA2 H 3.83 0.025 1 29 6 6 GLY HA3 H 3.83 0.025 1 30 7 7 LYS H H 8.08 0.0035 1 31 7 7 LYS HA H 4.12 0.025 1 32 7 7 LYS HB2 H 1.74 0.025 1 33 7 7 LYS HB3 H 1.74 0.025 1 34 7 7 LYS HD2 H 1.39 0.025 2 35 7 7 LYS HD3 H 1.47 0.025 2 36 7 7 LYS HE2 H 2.68 0.025 2 37 7 7 LYS HE3 H 3.45 0.025 2 38 7 7 LYS HG2 H 1.19 0.025 1 39 7 7 LYS HG3 H 1.19 0.025 1 40 7 7 LYS HZ H 8.07 0.0035 1 41 8 8 ARG H H 8.40 0.0035 1 42 8 8 ARG HA H 4.02 0.025 1 43 8 8 ARG HB2 H 1.74 0.025 1 44 8 8 ARG HB3 H 1.74 0.025 1 45 8 8 ARG HD2 H 3.08 0.025 1 46 8 8 ARG HD3 H 3.08 0.025 1 47 8 8 ARG HE H 7.12 0.0035 1 48 8 8 ARG HG2 H 1.51 0.025 2 49 8 8 ARG HG3 H 1.63 0.025 2 50 9 9 LYS H H 7.76 0.0035 1 51 9 9 LYS HA H 4.07 0.025 1 52 9 9 LYS HB2 H 1.76 0.025 1 53 9 9 LYS HB3 H 1.76 0.025 1 54 9 9 LYS HD2 H 1.61 0.025 2 55 9 9 LYS HD3 H 1.66 0.025 2 56 9 9 LYS HE2 H 2.89 0.025 1 57 9 9 LYS HE3 H 2.89 0.025 1 58 9 9 LYS HG2 H 1.28 0.025 2 59 9 9 LYS HG3 H 1.34 0.025 2 60 10 10 SER H H 8.23 0.0035 1 61 10 10 SER HA H 4.12 0.025 1 62 10 10 SER HB2 H 3.80 0.025 1 63 10 10 SER HB3 H 3.80 0.025 1 64 11 11 ASP H H 8.64 0.0035 1 65 11 11 ASP HA H 4.65 0.025 1 66 11 11 ASP HB2 H 2.62 0.025 2 67 11 11 ASP HB3 H 2.76 0.025 2 68 12 12 ARG H H 7.86 0.0035 1 69 12 12 ARG HA H 4.10 0.025 1 70 12 12 ARG HB2 H 1.79 0.025 1 71 12 12 ARG HB3 H 1.79 0.025 1 72 12 12 ARG HD2 H 3.09 0.025 1 73 12 12 ARG HD3 H 3.09 0.025 1 74 12 12 ARG HE H 7.16 0.0035 1 75 12 12 ARG HG2 H 1.59 0.025 1 76 12 12 ARG HG3 H 1.59 0.025 1 77 13 13 LYS H H 8.05 0.0035 1 78 13 13 LYS HA H 4.12 0.025 1 79 13 13 LYS HB2 H 1.77 0.025 1 80 13 13 LYS HB3 H 1.77 0.025 1 81 13 13 LYS HD2 H 1.61 0.025 1 82 13 13 LYS HD3 H 1.61 0.025 1 83 13 13 LYS HE2 H 2.90 0.025 1 84 13 13 LYS HE3 H 2.90 0.025 1 85 13 13 LYS HG2 H 1.32 0.025 2 86 13 13 LYS HG3 H 1.41 0.025 2 87 14 14 LYS H H 8.04 0.0035 1 88 14 14 LYS HA H 4.15 0.025 1 89 14 14 LYS HB2 H 1.82 0.025 1 90 14 14 LYS HB3 H 1.82 0.025 1 91 14 14 LYS HD2 H 1.75 0.025 1 92 14 14 LYS HD3 H 1.75 0.025 1 93 14 14 LYS HE2 H 2.69 0.025 2 94 14 14 LYS HE3 H 3.44 0.025 2 95 14 14 LYS HG2 H 1.24 0.025 2 96 14 14 LYS HG3 H 1.41 0.025 2 97 14 14 LYS HZ H 8.00 0.0035 1 98 15 15 LYS H H 8.22 0.0035 1 99 15 15 LYS HA H 4.01 0.025 1 100 15 15 LYS HB2 H 1.77 0.025 1 101 15 15 LYS HB3 H 1.77 0.025 1 102 15 15 LYS HD2 H 1.60 0.025 1 103 15 15 LYS HD3 H 1.60 0.025 1 104 15 15 LYS HG2 H 1.37 0.025 1 105 15 15 LYS HG3 H 1.37 0.025 1 106 16 16 ASN H H 7.88 0.0035 1 107 16 16 ASN HA H 4.50 0.025 1 108 16 16 ASN HB2 H 2.76 0.025 1 109 16 16 ASN HB3 H 2.76 0.025 1 110 17 17 GLN H H 8.21 0.0035 1 111 17 17 GLN HA H 4.05 0.025 1 112 17 17 GLN HB2 H 2.01 0.0035 1 113 17 17 GLN HB3 H 2.01 0.0035 1 114 17 17 GLN HG2 H 2.32 0.0035 1 115 17 17 GLN HG3 H 2.32 0.0035 1 116 18 18 ASP H H 8.30 0.0035 1 117 18 18 ASP HA H 4.59 0.025 1 118 18 18 ASP HB2 H 2.59 0.025 2 119 18 18 ASP HB3 H 2.81 0.025 2 120 18 19 NH2 HN1 H 7.24 0.0035 9 121 18 19 NH2 HN2 H 7.21 0.0035 9 stop_ save_ ######################## # Coupling constants # ######################## save_coupling_constant_list_1 _Saveframe_category coupling_constants _Details . loop_ _Experiment_label '2D 1H-1H NOESY' '2D 1H-1H TOCSY' '2D DQF-COSY' stop_ _Sample_conditions_label $sample_conditions_1 _Spectrometer_frequency_1H 600 _Mol_system_component_name 'nociceptin analogue' _Text_data_format . _Text_data . loop_ _Coupling_constant_ID _Coupling_constant_code _Atom_one_residue_seq_code _Atom_one_residue_label _Atom_one_name _Atom_two_residue_seq_code _Atom_two_residue_label _Atom_two_name _Coupling_constant_value _Coupling_constant_min_value _Coupling_constant_max_value _Coupling_constant_value_error 1 3JHNHA 2 GLY H 2 GLY HA 5.8 . . . 2 3JHNHA 3 GLY H 3 GLY HA 5.9 . . . 3 3JHNHA 4 PFF H 4 PFF HA 6.8 . . . 4 3JHNHA 5 THR H 5 THR HA 7.1 . . . 5 3JHNHA 6 GLY H 6 GLY HA 5.4 . . . 6 3JHNHA 7 LYS H 7 LYS HA 5.7 . . . 7 3JHNHA 8 ARG H 8 ARG HA 4.1 . . . 8 3JHNHA 9 LYS H 9 LYS HA 5.4 . . . 9 3JHNHA 10 SER H 10 SER HA 5.3 . . . 10 3JHNHA 11 ASP H 11 ASP HA 5.3 . . . 11 3JHNHA 12 ARG H 12 ARG HA 5.6 . . . 12 3JHNHA 13 LYS H 13 LYS HA 5.3 . . . 13 3JHNHA 14 LYS H 14 LYS HA 5.3 . . . 14 3JHNHA 15 LYS H 15 LYS HA 6.0 . . . 15 3JHNHA 16 ASN H 16 ASN HA 6.2 . . . 16 3JHNHA 17 GLN H 17 GLN HA 5.3 . . . 17 3JHNHA 18 ASP H 18 ASP HA 7.2 . . . stop_ save_